{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T13:53:06Z","timestamp":1767707586634,"version":"build-2065373602"},"reference-count":36,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T00:00:00Z","timestamp":1585699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Federal Ministry of Education and Research (BMBF)","award":["eBio-CIRSPLICE - FKZ031A316"],"award-info":[{"award-number":["eBio-CIRSPLICE - FKZ031A316"]}]},{"name":"Dr. Rolf M. Schwiete Stiftung","award":["2017"],"award-info":[{"award-number":["2017"]}]},{"name":"Congento","award":["LISBOA-01-0145-FEDER-022170"],"award-info":[{"award-number":["LISBOA-01-0145-FEDER-022170"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Malfunctions of circadian clock trigger abnormal cellular processes and influence tumorigenesis. Using an in vitro and in vivo xenograft model, we show that circadian clock disruption via the downregulation of the core-clock genes BMAL1, PER2, and NR1D1 impacts the circadian phenotype of MYC, WEE1, and TP53, and affects proliferation, apoptosis, and cell migration. In particular, both our in vitro and in vivo results suggest an impairment of cell motility and a reduction in micrometastasis formation upon knockdown of NR1D1, accompanied by altered expression levels of SNAI1 and CD44. Interestingly we show that differential proliferation and reduced tumour growth in vivo may be due to the additional influence of the host-clock and\/or to the 3D tumour architecture. Our results raise new questions concerning host\u2013tumour interaction and show that core-clock genes are involved in key cancer properties, including the regulation of cell migration and invasion by NR1D1 in zebrafish xenografts.<\/jats:p>","DOI":"10.3390\/cancers12040853","type":"journal-article","created":{"date-parts":[[2020,4,2]],"date-time":"2020-04-02T11:57:14Z","timestamp":1585828634000},"page":"853","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["The Core-Clock Gene NR1D1 Impacts Cell Motility In Vitro and Invasiveness in a Zebrafish Xenograft Colon Cancer Model"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0153-2784","authenticated-orcid":false,"given":"Alireza","family":"Basti","sequence":"first","affiliation":[{"name":"Institute for Theoretical Biology (ITB), Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt\u2014Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany"},{"name":"Molecular Cancer Research Center (MKFZ), Medical Department of Hematology, Oncology, and Tumor Immunology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt\u2014Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5550-2428","authenticated-orcid":false,"given":"Rita","family":"Fior","sequence":"additional","affiliation":[{"name":"Champalimaud Centre for the Unknown, Department of Experimental Clinical Research, Lisbon 1400-038, Portugal"}]},{"given":"M\u00fcge","family":"Yal\u04abin","sequence":"additional","affiliation":[{"name":"Institute for Theoretical Biology (ITB), Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt\u2014Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany"},{"name":"Molecular Cancer Research Center (MKFZ), Medical Department of Hematology, Oncology, and Tumor Immunology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt\u2014Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany"}]},{"given":"Vanda","family":"P\u00f3voa","sequence":"additional","affiliation":[{"name":"Champalimaud Centre for the Unknown, Department of Experimental Clinical Research, Lisbon 1400-038, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1179-4080","authenticated-orcid":false,"given":"Rosario","family":"Astaburuaga","sequence":"additional","affiliation":[{"name":"Institute for Theoretical Biology (ITB), Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt\u2014Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany"},{"name":"Molecular Cancer Research Center (MKFZ), Medical Department of Hematology, Oncology, and Tumor Immunology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt\u2014Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany"}]},{"given":"Yin","family":"Li","sequence":"additional","affiliation":[{"name":"Institute for Theoretical Biology (ITB), Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt\u2014Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany"},{"name":"Molecular Cancer Research Center (MKFZ), Medical Department of Hematology, Oncology, and Tumor Immunology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt\u2014Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4905-1207","authenticated-orcid":false,"given":"Julian","family":"Naderi","sequence":"additional","affiliation":[{"name":"Institute for Theoretical Biology (ITB), Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt\u2014Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany"},{"name":"Molecular Cancer Research Center (MKFZ), Medical Department of Hematology, Oncology, and Tumor Immunology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt\u2014Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8363-7183","authenticated-orcid":false,"given":"Miguel","family":"Godinho Ferreira","sequence":"additional","affiliation":[{"name":"Champalimaud Centre for the Unknown, Department of Experimental Clinical Research, Lisbon 1400-038, Portugal"},{"name":"Institute for Research on Cancer and Aging of Nice, INSERM U 1081, CNRS UMR7284 UNS, Universit\u00e9 C\u00f4te d\u2019Azur, 06107 Nice, France"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9165-2439","authenticated-orcid":false,"given":"Angela","family":"Rel\u00f3gio","sequence":"additional","affiliation":[{"name":"Institute for Theoretical Biology (ITB), Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt\u2014Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany"},{"name":"Molecular Cancer Research Center (MKFZ), Medical Department of Hematology, Oncology, and Tumor Immunology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt\u2014Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany"},{"name":"Institute of Systems Medicine and Bioinformatics, Department of Human Medicine, MSH Medical School Hamburg\u2014University of Applied Sciences and Medical University, 20457 Hamburg, Germany"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.cmet.2019.06.019","article-title":"Medicine in the Fourth Dimension","volume":"30","author":"Cederroth","year":"2019","journal-title":"Cell Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/B978-0-12-387690-4.00006-4","article-title":"Genetics of circadian rhythms in Mammalian model organisms","volume":"74","author":"Lowrey","year":"2011","journal-title":"Adv. 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